The circadian Clock mutation increases exploratory activity and escape-seeking behavior

Disturbances of circadian rhythms are associated with many types of mood disorders; however, it is unknown whether a dysfunctional circadian pacemaker can be the primary cause of altered emotional behavior. To test this hypothesis, male and female mice carrying a mutation of the circadian gene, Clock, were compared to wild-type mice in an array of behavioral tests used to measure exploratory activity, anxiety, and behavioral despair. Female Clock mutant mice exhibited significantly greater activity and rearing in an open field and a greater number of total arm entries in the elevated plus maze. In addition, female Clock mutant mice spent significantly more time swimming in the forced swim test than wild-type mice on both days of a 2-day test. Male Clock mutant mice also exhibited increased exploration of the open field and increased swimming in the forced swim test; however, behavioral changes were less robust in Clock mutant males compared to Clock mutant females. These changes in behavior were not dependent on the expression of a lengthened free-running period but were more or less striking depending on the testing conditions. These data indicate that the Clock mutation leads to increased exploratory behavior and increased escape-seeking behavior, and, conversely, does not result in increased anxiety or depressive-like behavior. These results suggest that the Clock gene is involved in regulating behavioral arousal, and that Clock may interact with sex hormones to produce these behavioral changes.     

The role of temperament in the relationship between morningness–eveningness and mood

Apart from differences in circadian phase position, individuals with different morningness–eveningness levels vary in many more characteristics. Particularly consistent relationships have been observed between morningness–eveningness and mood. Eveningness has been associated with disadvantageous mood, e.g. depressiveness in healthy individuals, and mood disorders. A concept of social jetlag suggests that evening subjects function in less advantageous environments due to discrepancies between internal and social time (societies promote morning-oriented functioning), which results in their lowered mood. Individual temperament, as defined by the Regulative Theory of Temperament (RTT), refers to the capacity of the human organism to meet environmental requirements – the greater the capacity, the less negative impact of external conditions. Thus, the aim of this study is to determine which RTT traits are linked to both morningness–eveningness and mood dimensions and to test whether they account for the relationship between morningness–eveningness and mood. A sample of 386 university students (267 female) aged between 19 and 47 (M?=?21.15, SD?=?4.23) years completed the University of Wales Institute of Science and Technology (UWIST) Mood Adjective Check List, Morningness–Eveningness Questionnaire and Formal Characteristics of Behaviour – Temperament Inventory. Analyses revealed lower endurance (EN) and higher emotional reactivity (ER) related to eveningness as well as to lower hedonic tone (HT), energetic arousal (EA) and to higher tense arousal (TA). Moreover, eveningness was associated with lower HT, EA and higher TA. Among RTT traits, EN was most strongly related to eveningness, and mediation analyses revealed that this temperamental trait fully mediated the relationship between eveningness and the three mood dimensions. The remaining RTT traits did not provide more explanation of the association between morningness–eveningness and mood than EN itself. If subjects did not differ in EN, the association between morningness–eveningness and mood was absent. EN is discussed as a protective factor against negative consequences of social jetlag and particularly lowered mood in evening individuals.     

Role of G‐proteins in the effects of leptin on pedunculopontine nucleus neurons

The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G‐protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole‐cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (I_Na) and h‐current (I_H) in PPN neurons. TA (100 nM) reduced the blockade of I_Na (~ 50% reduction) and I_H (~ 93% reduction) caused by leptin. Intracellular guanosine 5′‐[β‐thio]diphosphate trilithium salt (a G‐protein inhibitor) significantly reduced the effect of leptin on I_Na(~ 60% reduction) but not on I_H (~ 25% reduction). Intracellular GTPγS (a G‐protein activator) reduced the effect of leptin on both I_Na (~ 80% reduction) and I_H (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor‐ and G‐protein dependent. We also found that leptin enhanced NMDA receptor‐mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.

     

Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences,arousal regulation and sleep

Dopamine has been implicated in the regulation of sleep–wake states and the circadian rhythm. However, there is no consensus on the impact of two established dopaminergic gene variants: the catechol-O-methyltransferase Val158Met (COMT Val158Met; rs4680) and the dopamine D4 receptor Exon III variable-number-of-tandem-repeat polymorphism (DRD4 VNTR). Pursuing a multi-method approach, we examined their potential effects on circadian preferences, arousal regulation and sleep. Subjects underwent a 7-day actigraphy assessment (SenseWear Pro3), a 20-minute resting EEG (analyzed using VIGALL 2.0) and a body mass index (BMI) assessment. Further, they completed the Morningness–Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). The sample comprised 4625 subjects (19–82 years) genotyped for COMT Val158Met, and 689 elderly subjects (64–82 years) genotyped for DRD4 VNTR. The number of subjects varied across phenotypes. Power calculations revealed a minimum required phenotypic variance explained by genotype ranging between 0.5% and 1.5% for COMT Val158Met and between 3.3% and 6.0% for DRD4 VNTR. Analyses did not reveal significant genotype effects on MEQ, ESS, PSQI, BMI, actigraphy and EEG variables. Additionally, we found no compelling evidence in sex- and age-stratified subsamples. Few associations surpassed the threshold of nominal significance (p < .05), providing some indication for a link between DRD4 VNTR and daytime sleepiness. Taken together, in light of the statistical power obtained in the present study, our data particularly suggest no impact of the COMT Val158Met polymorphism on circadian preferences, arousal regulation and sleep. The suggestive link between DRD4 VNTR and daytime sleepiness, on the other hand, might be worth investigation in a sample enriched with younger adults.     

Role of electroencephalogram and oxygen saturation in the induction mechanism of arousal for obstructive sleep apnea-hypopnea syndrome patients

Arousal concomitant with obstructive sleep apnea-hypopnea syndrome (OSAHS) is known to result in sleep fragmentation and excessive daytime sleepiness. The cause of arousal is multifarious, and the mechanism is not yet clear. The aim of this study was to further research the induction mechanism of arousal by investigating the variation of electroencephalogram (EEG) and oxygen saturation (SaO₂). This study enrolled 20 subjects with a clinical diagnosis of OSAHS who underwent overnight polysomnography. Respiratory events and arousals were scored, and individuals with insufficient samples (<30) were excluded. Thus, 13 subjects mostly with severe OSAHS were analyzed in this study. The wavelet coefficients, spectral power of EEG (C4-M1 and C3-M2) before arousal or airway reopening, and the maximum desaturations of SaO₂ during respiratory events were analyzed. For most subjects, EEG (in stages N1 and N2) during respiratory events with arousals exhibited significantly lower values of wavelet coefficients and spectral power (p < 0.05). The maximum desaturations of SaO₂ during respiratory events with arousals are larger than those without among individual. In binary logistic regression analysis, the P values of EEG features and SaO₂ desaturation were both less than 0.001. Our results demonstrate that in light NREM stage, less activity in EEG during respiratory events and larger SaO₂ drop both independently were related to the occurrence of arousal. These significant differences come from major subjects based on the statistical analysis, and help supplement the induction mechanism of arousal.     

注意缺陷多动障碍低觉醒模型的新证据

注意缺陷多动障碍（Attention Deficit Hyperactivity Disorder,ADHD）是儿童期常见的一种发展性的异常,其病因及发生机理至今未明。低觉醒模型是ADHD成因的一种假设。本文从睡眠障碍导致的低觉醒探讨ADHD发生机理。通过对ADHD儿童的睡眠障碍进行分析以及将ADHD外在表现与睡眠剥夺后的表现进行对比分析,得出ADHD儿童存在的低觉醒是由于外显的或内隐的睡眠障碍引起的,一方面间接证明了低觉醒模型,另一方面为ADHD的成因研究开拓了新的思路。     

Mice Reach Higher Visual Sensitivity at Night by Using a More Efficient Behavioral Strategy

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Advertising individual identity by mother and adolescent contact calls in Siberian wapiti Cervus elaphus sibiricus

Individualistic contact calls facilitate mother‐offspring reunion after separation. However, in many mammals, both the acoustic structure and individuality of contact calls differ between mother and young. In contrast, in Siberian wapiti Cervus elaphus sibiricus, contact calls are similar in the acoustics between mother and young, whereas effects of this similarity on vocal individuality were not investigated. In this study, we analyzed acoustic differences between closed‐mouth (nasal) and open‐mouth (oral) contact calls and examined individuality of the most usual oral calls of 19 Siberian wapiti (9 hinds and 10 5–6‐month adolescents) emitted in response to mother‐offspring separation. In the oral calls, the values of frequency and power variables were higher than in the nasal calls. Calls of hinds and adolescents did not differ by the maximum fundamental frequency and duration, whereas the peak frequency was higher in the young. Discriminant function analysis (DFA) based on 11 acoustic variables of oral calls accurately classified to individual 92.5% of hind calls and 96.9% of adolescent calls (chi‐square test for differences between hinds and adolescents, p = 0.19). Variables mainly contributing to vocal identity (duration, start, and maximum fundamental frequency) were the same in calls of mothers and adolescents. We conclude that similarities in the acoustics calls of mothers and adolescents mean that they do not differ in their potential for encoding individual identity, suggesting a mutual process of mother‐offspring vocal recognition in Siberian wapiti.     

Recurrent Circuitry for Balancing Sleep Need and Sleep

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